• Archives of Pharmacal Research
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• v.20 no.6
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• pp.539-544
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• 1997

Anti-metastatic activities of IH901, an intestinal bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo. Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT 1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3907-3912
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• 2015

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.759-764
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• 2013

Background: The high recurrence rate after hepatic resection in hepatocellular carcinoma (HCC) is a major obstacle to improving prognosis. The objective of the present study was to explore the function of genistein, a soy-derived isoflavone, in enhancing the inhibitory effect of cisplatin on HCC cell proliferation and on tumor recurrence and metastasis in nude mice after curative hepatectomy. Methods: Proliferation of human HCC cells (HCCLM3) was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Synergistic effects of genistein and cisplatin were evaluated with the median-effect formula. Nude mice bearing human HCC xenografts underwent tumour resection (hepatectomy) 10 days post implantation, then received intraperitoneal administration of genistein or cisplatin alone or the combination of the two drugs. 33 days after surgery, recurrent tumours and pulmonary metastasis were evaluated individually. MMP-2 level in recurrent tumours was detected by immunohistochemistry and real-time PCR; MMP-2 expression in HCCLM3 was detected by immunocytochemistry. Results: Genistein and cisplatin both suppressed the growth and proliferation of HCCLM3 cells. The two drugs exhibited synergistic effects even at relatively low concentrations. In vivo, mice in the combined genistein and cisplatin group had a smaller volume of liver recurrent tumors and fewer pulmonary metastatic foci compared with single drug treated groups. Cisplatin upregulated the expression of MMP-2 in both recurrent tumours and HCCLM3, while genistein abolished cisplatin-induced MMP-2 expression. Conclusions: Genistein reinforced the inhibitory effect of cisplatin on HCC cell proliferation and tumour recurrence and metastasis after curative hepatectomy in nude mice, possibly through mitigation of cisplatin-induced MMP-2 upregulation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4255-4261
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• 2012

The present study was conducted to evaluate radioimmunoimaging (RII) and in vivo distribution of mixed antibodies $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb in nude mice bearing human lung adenocarcinoma xenografts. Single and mixed applications of the two radiolabeled monoclonal antibodies (mAbs) were compared. Direct labeling of $^{99m}Tc$ was applied to radiolabel the EGFR and CD44 mAbs. The properties of the radiolabeled antibodies were then characterized. RII and assessment of the distribution of the antibodies in nude mice bearing lung adenocarcinoma xenografts were achieved by applying separate and combined doses of $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb. The labeling rates of $^{99m}Tc$ for EGFR-mAb and CD44-mAb were $91.5%{\pm}3.8%$ and $92.3%{\pm}4.1%$ respectively, with specific activities of 2.8 and $2.9MBq/{\mu}g$, respectively, and radiochemical purities (RCP) of 96.5% and 96.2%. The radioactivity uptake of the combined application of both radiolabeled antibodies was clearly higher than with a single application of either alone. The relative values of target-to-nontarget (T/NT) measured through the regional interest (ROI) technique were $5.59{\pm}0.42$ (mixed antibodies), $2.78{\pm}0.20$ ($^{99m}Tc$-EGFR-mAb), and $2.28{\pm}0.16$ ($^{99m}Tc$-CD44-mAb) in the RII. The body distribution of the radiolabeled antibodies and their imaging results were basically identical. Application of the mixed antibodies with $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb can increase the radioactivity uptake of tumor tissue, leading to more ideal target-to-nontarget ratios, and therefore superior results.

• Journal of Food Hygiene and Safety
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• v.4 no.2
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• pp.109-118
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• 1989

To find antitumor components in the cultured mycelia of Lepiota procera, the proteinpolysaccharide obtained from the mycelia was subjected to DEAE - Sephadex A-50 column chromatography and Sepharose-4B gel filtration. Of the fractions, the purified Fraction C1 was named lepiotan and examined for antitumor activity against the solid form of sarcoma 180 in ICR mice. The inhibition ratio of lepiotan was 64% at the dose of 10 mg/kg/day for 10days. The chemical analysis of lepiotan showed 60% polysaccharide and 21 % protein. The polysaccharide moiety was found to be a heteromannoglucan which consisted of 46.3% glucose, 40.2% mannose and 11.0% fucose. When the antitumor component, Fraction A, was examined for immunopotentiation activity, it was found to increase the number of plaques in hemolytic plaque assay and to restore the immunity in the tumor-bearing mice up to 89.7% of the normal level. Also the antitumor acitivity was suppressed by the treatment with carrageenan, an antimacrophage agent. These results indicate that the antitumor activity was exerted through immunopotentiation, but not through direct cytotoxicity against the tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3351-3355
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• 2013

Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dosedependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.377-385
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• 2014

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

• Toxicological Research
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• v.27 no.2
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• pp.77-83
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• 2011

The objective of this study was to evaluate and compare the antitumor activity of different solvent fractions (ethanol, dichloromethane, ethyl acetate, butanol and water) of the Auricularia auricula-judae 70% ethanol extract on the P388D1 macrophage and sarcoma 180 cells. A dose-dependent antitumor activity of each solvent fraction (from 0.01 mg/ml to 0.3 mg/ml) was shown against both cell types. These cytotoxic effects of all the tested fractions were confirmed on the MTT and SRB assays, without statistical differences each other. $IC_{50}$ value of dichloromethane fraction was 94.2 ${\mu}g/ml$ against sarcoma 180 cells lower than any other solvent fractions. The potent antitumor effect of the dichloromethane (DCM) fraction was also found against solid tumor in BALB/c mice. The splenomegaly and higher splenic index were found in tumor-bearing mice, with the DCM fraction returning to the negative control values. Thus, the results indicated the dichloromethane fraction may have potential ingredients as antitumor candidates.

• Macromolecular Research
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• v.16 no.6
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• pp.510-516
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• 2008

New antitumor active polymers, poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalic acid) [poly(MTCA-co-ETAc)], poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-hydrogen ethyl-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalate) [poly(MTCA-co-HEET)], and poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-a-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(MTCA-co-EETFU)] were synthesized and characterized. Their antitumor activity, inhibition of DNA replication and antiangiogenesis were examined. The structures of the polymers were identified by FT-IR, $^1H$ and $^{13}C$-NMR spectroscopy. The number average molecular weights of the fractionated polymers determined by GPC ranged from 9,400 to 14,900, and polydispersity indices were less than 1.7. The in vitro cytotoxicity of these polymers was determined and their antitumor activity was evaluated. The $IC_{50}$ values (the drug concentration at inhibition of 50% tumor growth) indicated that the synthesized polymers were much better inhibitors of cancer cells and showed lower cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined using mice bearing the sarcoma 180 tumor cell line. The life spans (TIC) of the mice treated with the conjugates were higher than those treated with the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity based on an embryo chorioallantoic membrane assay.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.2
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• pp.372-376
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• 2001

The effect of garlic extract and vitamin C mixture on the various cancer cell lines in vitro and in vivo have been examined. Proliferation of human colon cancer (HT-29), human rectal cancer (HRT-18) and human hepatoma (HepG2) cells was inhibited by garlic extract and vitamin C, respectively. Based on the cytotoxic activity, mixture of garlic extract and vitamin C was demonstrated to possess a synergistic growth inhibition on HT-29, HRT-18 and HepG2 cancer cells. Mixture of garlic extract and vitamin C significantly arrested G2/M phase cells in the HepG2 cell cycle. Oral administration of mixture of garlic extract and vitamin C to sarcoma-180 tumor-bearing mice prolonged survival time compared to that of control group. These results suggested that addition of vitamin C enhances anticancer activity of garlic extract in vitro, and mixture of garlic extract and vitamin C has antitumor effect in vivo.